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Pulmonary drug delivery

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https://www.readbyqxmd.com/read/28095918/anti-staphylococcal-activity-resulting-from-epithelial-lining-fluid-elf-concentrations-of-amikacin-inhale-administered-via-the-pulmonary-drug-delivery-system
#1
Islam M Ghazi, Mordechai Grupper, David P Nicolau
BACKGROUND: Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections...
January 17, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28093351/in-vitro-uptake-and-transport-studies-of-peg-plga-polymeric-micelles-in-respiratory-epithelial-cells
#2
Xiao Hu, Fei-Fei Yang, Chun-Yu Liu, Carsten Ehrhardt, Yong-Hong Liao
Polymeric micelles are considered promising carriers for pulmonary drug delivery. Their interaction with the respiratory epithelium, however, is mostly unknown. In the present study, methoxypoly (ethylene glycol) (mPEG)-poly (lactic-co-glycolic acid) (PLGA) micelles containing curcumin acetate (CA) or a mixture of CA and Nile Red (NR) were prepared using the solvent evaporation method. Calu-3 and NCI-H441 human respiratory epithelial cell monolayers were used as in vitro models of upper and lower respiratory tract epithelium barrier, respectively, to study the cellular uptake and transport of the vesicles...
January 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088005/nicotine-hydrogen-tartrate-loaded-chitosan-nanoparticles-formulation-characterization-and-in-vitro-delivery-from-dry-powder-inhaler-formulation
#3
Hui Wang, Graeme George, Selena Bartlett, Changyou Gao, Nazrul Islam
This study reports the development of nanoparticles in the form of inhalable micro-aggregates of biodegradable chitosan (CS) loaded with nicotine hydrogen tartrate (NHT) for potential pulmonary delivery of nicotine from dry powder inhaler (DPI) formulations with prolonged release profile. The NHT-loaded CS particles were prepared using a water-in-oil emulsion crosslinking method. The prepared particles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for morphological studies; Zetasizer and Mastersizer were applied for particle size analysis...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28078950/magnetic-nanoparticles-based-drug-and-gene-delivery-systems-for-the-treatment-of-pulmonary-diseases
#4
Ibrahim M El-Sherbiny, Nancy M Elbaz, Mohammed Sedki, Abdulaziz Elgammal, Magdi H Yacoub
Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer...
January 12, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28070713/porous-mannitol-carrier-for-pulmonary-delivery-of-cyclosporine-a-nanoparticles
#5
Sharon Shui Yee Leung, Jennifer Wong, Heloisa Victorino Guerra, Kevin Samnick, Robert K Prud'homme, Hak-Kim Chan
This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28066140/metabolism-and-excretion-of-novel-pulmonary-targeting-docetaxel-liposome-in-rabbits
#6
Jie Wang, Li Zhang, Lijuan Wang, Zhonghong Liu, Yu Yu
Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultraperformance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28043593/new-approaches-in-drug-treatment-for-tuberculosis-inhalation-using-liposomes-only-a-future-vision-or-soon-in-clinical-practice
#7
Lars-Olof Larsson
A major change of therapy in respiratory medicine has been the transition from oral or parenteral to inhalation therapy, for example, in asthma. Inhalation of anti-infectious drugs has however not a key-role in the treatment of pulmonary infections such as tuberculosis (TB). The inhalation therapy provides several benefits; the target is reached directly with evasion of first-pass metabolism, thereby resulting in reduced systemic side effects. Furthermore, the drug is delivered to an extensive surface area that is rich in lymphoid tissue...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28040495/tips-pentacene-loaded-peo-pdlla-core-shell-nanoparticles-have-similar-cellular-uptake-dynamics-in-m1-and-m2-macrophages-and-in-corresponding-in-vivo-microenvironments
#8
Dylan K McDaniel, Ami Jo, Veronica M Ringel-Scaia, Sheryl Coutermarsh-Ott, Daniel E Rothschild, Michael Powell, Rui Zhang, Timothy E Long, Kenneth Oestreich, Judy S Riffle, Richey M Davis, Irving C Allen
Nanoparticle based drug delivery platforms have the potential to transform disease treatment paradigms and therapeutic strategies, especially in the context of pulmonary medicine. Once administered, nanoparticles disperse throughout the lung and many are phagocytosed by macrophages. However, there is a paucity of knowledge regarding cellular up-take dynamics of nanoparticles due largely to macrophage heterogeneity. To address this issue, we sought to better define nanoparticle up-take using polarized M1 and M2 macrophages and novel TIPS-pentacene loaded PEO-PDLLA nanoparticles...
December 28, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28039077/pharmacokinetics-of-tiotropium-administered-by-respimat-%C3%A2-in-asthma-patients-analysis-of-pooled-data-from-phase-ii-and-iii-clinical-trials
#9
Ashish Sharma, Huib A M Kerstjens, René Aalbers, Petra Moroni-Zentgraf, Benjamin Weber, Ronald Dahl
Tiotropium is a long-acting inhaled antimuscarinic bronchodilator that has recently received marketing authorization for the indication of asthma with dose delivery via the Respimat(®) inhaler, in addition to its widely established role in the management of chronic obstructive pulmonary disease (COPD). This report presents a combined analysis of tiotropium plasma and urine pharmacokinetics at steady state from 8 Phase II/III clinical trials in asthma and delineates the effects of patient characteristics on systemic exposure based on the parameters fe0-24,ss (fraction of dose excreted unchanged in urine over 24 h post-dose at steady-state) and dose-normalized AUCtau,ss and Cmax,ss...
December 27, 2016: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28013164/polymeric-drug-delivery-micelle-like-nanocarriers-for-pulmonary-administration-of-beclomethasone-dipropionate
#10
D Triolo, E F Craparo, B Porsio, C Fiorica, G Giammona, G Cavallaro
In this paper, the potential of novel polymeric micelles as drug delivery systems for Beclomethasone Dipropionate (BDP) administration into the lung is investigated. These nanostructures are obtained starting from α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA), which was subsequently functionalized with O-(2-aminoethyl)-O'-methylpolyethylenglycole (PEG2000), ethylenediamine (EDA) and lipoic acid (LA), obtaining PHEA-PEG2000-EDA-LA graft copolymer. Empty and drug-loaded micelles possess adequate chemical-physical characteristics for pulmonary administration such as spherical shape, slightly positive surface charge and mean size of about 200nm...
December 9, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28009603/crospovidone-and-microcrystalline-cellulose-a-novel-description-of-pharmaceutical-fillers-in-the-gastrointestinal-tract
#11
Sophia M Shaddy, Michael A Arnold, Konstantin Shilo, Wendy L Frankel, Alan E Harzman, Peter P Stanich, Aatur D Singhi, Martha M Yearsley, Christina A Arnold
Crospovidone and microcrystalline cellulose (MCC) are pharmaceutical fillers well known in the pulmonary pathology literature. Fillers are inactive substances incorporated into medications to facilitate drug delivery. By examining 545 consecutive gastrointestinal surgical specimens from 302 patients between September 11, 2015 and October 23, 2015, we identified the fillers in 29 specimens from 26 patients. The control group consisted of an equal number of consecutive site-matched specimens collected during this same time...
December 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28004591/long-acting-muscarinic-antagonists-for-the-treatment-of-chronic-obstructive-pulmonary-disease-a-review-of-current-and-developing-drugs
#12
Mark A Mastrodicasa, Christopher A Droege, Aaron M Mulhall, Neil E Ernst, Ralph J Panos, Muhammad A Zafar
Long acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction by antagonizing para-sympathetic bronchoconstricting effects within the airways. For years, tiotropium, has been the cornerstone LAMA for chronic obstructive pulmonary disease (COPD) management. Recently, new agents, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide, have been developed and introduced into clinical practice. Areas Covered: This article reviews the clinical efficacy and adverse effects of currently available LAMAs in COPD treatment as well as developing LAMAs in early clinical trials and preclinical studies (V0162, TD-4208, CHF 5407, AZD9164, AZD8683, bencycloquidium)...
December 22, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27999290/validation-and-application-of-an-ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-yuanhuacine-determination-in-rat-plasma-after-pulmonary-administration-pharmacokinetic-evaluation-of-a-new-drug-delivery-system
#13
Man Li, Xiao Liu, Hao Cai, Zhichun Shen, Liu Xu, Weidong Li, Li Wu, Jinao Duan, Zhipeng Chen
Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to alleviate the adverse toxicity effects, we tried to deliver yuanhuacine directly into the lungs. Ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to detect the analyte and IS. After extraction (ether:dichloromethane = 8:1), the analyte and IS were separated on a Waters BEH-C18 column (100 mm × 2...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27991644/pulmonary-surfactant-protein-sp-d-opsonises-carbon-nanotubes-and-augments-their-phagocytosis-and-subsequent-pro-inflammatory-immune-response
#14
Kirsten M Pondman, Basudev Paudyal, Robert B Sim, Anuvinder Kaur, Lubna Kouser, Anthony G Tsolaki, Lucy A Jones, Carolina Salvador-Morales, Haseeb A Khan, Bennie Ten Haken, Gudrun Stenbeck, Uday Kishore
Carbon nanotubes (CNTs) are increasingly being developed for use in biomedical applications, including drug delivery. One of the most promising applications under evaluation is in treating pulmonary diseases such as tuberculosis. Once inhaled or administered, the nanoparticles are likely to be recognised by innate immune molecules in the lungs such as hydrophilic pulmonary surfactant proteins. Here, we set out to examine the interaction between surfactant protein D (SP-D), a key lung pattern recognition molecule and CNTs, and possible downstream effects on the immune response via macrophages...
January 19, 2017: Nanoscale
https://www.readbyqxmd.com/read/27988327/nanocrystals-embedded-in-chitosan-based-respirable-swellable-microparticles-as-dry-powder-for-sustained-pulmonary-drug-delivery
#15
Rui Ni, Jing Zhao, Qiaoyu Liu, Zhenglin Liang, Uwe Muenster, Shirui Mao
In this study, nanocrystals embedded in microparticles were designed to achieve sustained pulmonary drug delivery of hydrophobic drugs. Chitosan based microparticles were engineered to allow sustained drug release via swelling and mucoadhesive properties of the polymer. Taking cinaciguat as a hydrophobic model drug, drug nanocrystals were prepared by high pressure homogenization and then encapsulated in chitosan microparticles via spray drying. Through various in vitro characterizations, it was shown that drug loaded microparticles had a high drug loading with promising aerosolization characteristics (mean volume diameter (Dv50) 3-4μm, experimental mass mean aerodynamic diameter (MMADe) 4-4...
December 15, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27987794/bioflavonoid-hesperetin-overcome-bicalutamide-induced-toxicity-by-co-delivery-in-novel-snedds-formulations-optimization-in-vivo-evaluation-and-uptake-mechanism
#16
Abhishek Arya, Hafsa Ahmad, Sachin Tulsankar, Satish Agrawal, Naresh Mittapelly, Rajkumar Boda, Rabi S Bhatta, Kalyan Mitra, Anil K Dwivedi
In the present study, we designed Bicalutamide (BCT) and Hesperetin (HSP) co-loaded self nano-emulsifying drug delivery system (SNEDDS) to encounter the problem of BCT induced toxicity, low solubility, and bioavailability. Optimized BCT-HSP SNEDDS would produce an emulsion of globule size 30.84±1.24nm with a high encapsulation efficiency of BCT (91.29%) and HSP (88.19%), and showed rapid drug release. DPPH assay confirmed the retention of antioxidant potential of HSP in SNEDDS. DCFH-DA confirmed intense green fluorescence in HSP treated groups due to the generation of reactive oxygen species...
February 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/27979766/nebulized-solid-lipid-nanoparticles-for-the-potential-treatment-of-pulmonary-hypertension-via-targeted-delivery-of-phosphodiesterase-5-inhibitor
#17
Shaimaa Makled, Noha Nafee, Nabila Boraie
Phosphodiesterase type 5 (PDE-5) inhibitors - among which sildenafil citrate (SC) - play a primary role in the treatment of pulmonary hypertension (PH). Yet, SC can be only administered orally or parenterally with lot of risks. Targeted delivery of SC to the lungs via inhalation/nebulization is mandatory. In this study, solid lipid nanoparticles (SLNs) loaded with SC were prepared and characterized in terms of colloidal, morphological and thermal properties. The amount of drug loaded and its release behavior were estimated as a function of formulation variables...
December 12, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27978796/neuropathic-pain-and-lung-delivery-of-nanoparticulate-drugs-an-emerging-novel-therapeutic-strategy
#18
Nazrul Islam, Muzaffar Abbas, Shafiqur Rahman
Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance...
December 12, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27977216/inhalation-of-respirable-crystalline-rifapentine-particles-induces-pulmonary-inflammation
#19
Thaigarajan Parumasivam, Anneliese S Ashhurst, Gayathri Nagalingam, Warwick J Britton, Hak-Kim Chan
Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27973764/aerosol-delivery-of-functionalized-gold-nanoparticles-target-and-activate-dendritic-cells-in-a-3d-lung-cellular-model
#20
Kleanthis Fytianos, Savvina Chortarea, Laura Rodriguez-Lorenzo, Fabian Blank, Christophe von Garnier, Alke Petri-Fink, Barbara Rothen-Rutishauser
Nanocarrier design combined with pulmonary drug delivery holds great promise for the treatment of respiratory tract disorders. In particular, targeting of dendritic cells that are key immune cells to enhance or suppress an immune response in the lung is a promising approach for the treatment of allergic diseases. Fluorescently encoded poly(vinyl alcohol) (PVA)-coated gold nanoparticles, functionalized with either negative (-COO(-)) or positive (-NH3(+)) surface charges, were functionalized with a DC-SIGN antibody on the particle surface, enabling binding to a dendritic cell surface receptor...
December 19, 2016: ACS Nano
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